Scientists discover novel therapeutic strategy for FLT3-ITD-positive acute myeloid leukemia

A new type of targeting chaperon protein HSP70 inhibitor QL47 was recently discovered by a team led by Prof. LIU Qingsong from the Hefei Institutes of Physical Science (HFIPS) of the Chinese Academy of Sciences to treat FLT3-ITD-positive acute myeloid leukemia (AML). Their findings have been published on Signal Transduction and Targeted Therapy.

What we are seeking is a new therapeutic strategy which imperative for FLT3-ITD-positive AML."

Hu Chen, Study's Lead Author

Approximately, 25% of AMLs carry FLT3-ITD (internal tandem duplication) oncogenic mutations, and FLT3 kinase inhibitors have already achieved great success in the clinic for FLT3-ITD-positive AML. However, after prolonged treatment, drug-acquired resistance is observed in patients treated with FLT3 kinase inhibitor.

In this research, the researchers found that compound QL47 had potent anti-proliferative activity against FLT3-ITD positive AML cell lines and induces FLT3-ITD protein degradation.

Further study proved that QL47 irreversibly bound to the heat shock protein HSP70 and inhibited its refolding activity, which in turn led to the degradation of FLT3-ITD and inhibited proliferation of the FLT3-ITD positive AML cells.

"It is inducible HSP70 instead of constitutive expressed HSC70 that is important for FLT3 protein stabilization and FLT3-ITD-positive cell viability," said Dr. HU.

The evaluation of QL47 in primary patient cells and in vivo tumor models showed that QL47 induced the degradation of FLT3-ITD protein and cell apoptosis in primary patient cells. In mice bone marrow engraftment model, QL47 significantly extends the animal survivals.

"Targeting the chaperone protein HSP70 could potentially provide a novel strategy for FLT3-ITD-positive AML treatment," said HU.

Journal reference:

Hu, C., et al. (2021) Targeting chaperon protein HSP70 as a novel therapeutic strategy for FLT3-ITD-positive acute myeloid leukemia. Signal Transduction and Targeted Therapy.


The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of News Medical.
Post a new comment

While we only use edited and approved content for Azthena answers, it may on occasions provide incorrect responses. Please confirm any data provided with the related suppliers or authors. We do not provide medical advice, if you search for medical information you must always consult a medical professional before acting on any information provided.

Your questions, but not your email details will be shared with OpenAI and retained for 30 days in accordance with their privacy principles.

Please do not ask questions that use sensitive or confidential information.

Read the full Terms & Conditions.

You might also like...
Innovative therapy targets and destroys leukemia stem cells